Abstract 945: Early detection of high-grade IPMN using extracellular vesicles - a successful patient story
Authors: Harmeet Dhani, Juan Hinestrosa, Heath I. Balcer, Edward Nolan, Razelle Kurzrock, Paul Billings
Journal: Cancer Research (2023)

Abstract Background/Purpose The detection of pancreatic ductal adenocarcinoma (PDAC) lesions at pre-cancerous or early-stages is critical to improving patient survival. The rise of liquid biopsies could potentially fill this unmet clinical need, such as our recently developed pancreatic LDT which isolates extracellular vesicles (EVs) from blood for detection of PDAC at earlier stages. In this case study, we describe a 60-year-old healthy male with acute pancreatitis who underwent an extensive imaging work-up that failed to detect radiographic evidence of lesions prior to surgery. Results from our EV-based early detection blood test, previously reported to have a specificity of 91.1% and sensitivity of 95.7% for stage I/II PDAC, indicated a high likelihood of PDAC. Subsequent pathology review after Whipple surgery confirmed high-grade intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasms (PanINs). Case Description The patient was brought to the clinic for persistent abdominal bloating and pressure. A CT scan of the abdomen and an elevated lipase yielded a diagnosis of first episode of acute pancreatitis. Two MRIs of the abdomen confirmed an abnormal pancreatic duct dilatation, but no evident masses. An endoscopic ultrasound later demonstrated an abrupt stricture of the pancreatic duct. Due to complete duct occlusion, an endoscopic retrograde cholangiopancreatography (ERCP) was performed with stent placement. Cytology brushings from the ERCP were non-diagnostic, and CA-19-9 and CEA were non-elevated. The patient sought additional genetic analysis on his captured cyst fluid cells, which showed mutations in K-RAS and p53, raising clinical concern. Testing with a DNA-methylation test for cancer detection reported a result of “No Cancer Signal Detected”; however, blood testing with our EV-based early detection blood test indicated a high probability of PDAC. The patient decided to undergo a Whipple procedure. The final surgical pathology revealed a main-duct high-grade dysplasia IPMN with PanINs. Recovery post-surgery was unremarkable. Discussion This case report illustrates the successful clinical utility of an EV-based blood assay for detection of high-grade IPMN and PanINs, lesions not identified through extensive imaging workup lesion and destined, with high probability (~60-70%), to progress to a pancreatic cancer. The eventual impetus for this patient to undergo surgery was the combination of his known pancreatic duct pathology and other clinicopathological characteristics, with the results of the EV-based liquid biopsy test acting as an adjunct clinical tool to support to his decision. Conclusions PDAC is a lethal malignancy with a long-term survival of &amp;lt;10%. Detection at the earliest stage can be associated with &amp;gt;80% survival. A prospective, multi-center, observational registry study - ExoLuminate - is underway to further evaluate patients at high-risk for PDAC. Citation Format: Harmeet Dhani, Juan Hinestrosa, Heath I. Balcer, Edward Nolan, Razelle Kurzrock, Paul Billings. Early detection of high-grade IPMN using extracellular vesicles - a successful patient story [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 945.